The New Vision for Genome Research Unveiled
from: http://www.genome.gov/11006929
International Consortium Completes Human Genome
Project
All Goals Achieved; New Vision for Genome Research
Unveiled
BETHESDA, Md., April 14, 2003 - The International
Human Genome Sequencing Consortium, led in the United
States by the National Human Genome Research Institute
(NHGRI) and the Department of Energy (DOE), today
announced the successful completion of the Human
Genome Project more than two years ahead of schedule.
Also today, NHGRI unveiled its bold new vision for the
future of genome research, officially ushering in the
era of the genome. The vision will be published in the
April 24 issue of the journal Nature, coinciding with
the 50th anniversary of Nature's publication of the
landmark paper by Nobel Laureates James Watson and
Francis Crick that described DNA's double helix. Dr.
Watson also was the first leader of the Human Genome
Project
The international effort to sequence the 3 billion DNA
letters in the human genome is considered by many to
be one of the most ambitious scientific undertakings
of all time, even compared to splitting the atom or
going to the moon.
"The Human Genome Project has been an amazing
adventure into ourselves, to understand our own DNA
instruction book, the shared inheritance of all
humankind," said NHGRI Director Francis S. Collins,
M.D., Ph.D., leader of the Human Genome Project since
1993. "All of the project's goals have been completed
successfully - well in advance of the original
deadline and for a cost substantially less than the
original estimates."
Aristides Patrinos, Ph.D., director of DOE's Office of
Biological and Environmental Research in the Office of
Science, said, "Sequencing the human genome was a
pioneering venture with risks and uncertainties. But
its success has created a revolution - transforming
biological science far beyond what we could imagine.
We have opened the door into a vast and complex new
biological landscape. Exploring it will require even
more creative thinking and new generations of
technologies."
The flagship effort of the Human Genome Project has
been producing the reference sequence of the human
genome. The international consortium announced the
first draft of the human sequence in June 2000. Since
then, researchers have worked tirelessly to convert
the "draft" sequence into a "finished" sequence.
Finished sequence is a technical term meaning that the
sequence is highly accurate (with fewer than one error
per 10,000 letters) and highly contiguous (with the
only remaining gaps corresponding to regions whose
sequence cannot be reliably resolved with current
technology). That standard was first achieved for a
human chromosome when a team of British, Japanese and
U.S. researchers produced a finished sequence for
human chromosome 22 in 1999.
The finished sequence produced by the Human Genome
Project covers about 99 percent of the human genome's
gene-containing regions, and it has been sequenced to
an accuracy of 99.99 percent. In addition, to help
researchers better understand the meaning of the human
genetic instruction book, the project took on a wide
range of other goals, from sequencing the genomes of
model organisms to developing new technologies to
study whole genomes. As of April 14, 2003, all of the
Human Genome Project's ambitious goals have been met
or surpassed.
When the Human Genome Project was launched in 1990,
many in the scientific community were deeply skeptical
about whether the project's audacious goals could be
achieved, particularly given its hard-charging
timeline and relatively tight spending levels. At the
outset, the U.S. Congress was told the project would
cost about $3 billion in FY 1991 dollars and would be
completed by the end of 2005. In actuality, the Human
Genome Project was finished two and a half years ahead
of time and, at $2.7 billion in FY 1991 dollars,
significantly under original spending projections
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"Never would I have dreamed in 1953 that my scientific
life would encompass the path from DNA's double helix
to the 3 billion steps of the human genome. But when
the opportunity arose to sequence the human genome, I
knew it was something that could be done - and that
must be done," said Nobel Laureate James D. Watson,
Ph.D., president of Cold Spring Harbor Laboratory in
Cold Spring Harbor, N.Y. "The completion of the Human
Genome Project is a truly momentous occasion for every
human being around the globe."
Besides delivering on the stated goals, the
international network of researchers has produced an
amazing array of advances that most scientists had not
expected until much later. These "bonus"
accomplishments include: an advanced draft of the
mouse genome sequence, published in December 2002; an
initial draft of the rat genome sequence, produced in
November 2002; the identification of more than 3
million human genetic variations, called single
nucleotide polymorphisms (SNPs); and the generation of
full-length complementary DNAs (cDNAs) for more than
70 percent of known human and mouse genes.
The International Human Genome Sequencing Consortium
included hundreds of scientists at 20 sequencing
centers in China, France, Germany, Great Britain,
Japan and the United States. The five institutions
that generated the most sequence were: Baylor College
of Medicine, Houston; Washington University School of
Medicine, St. Louis; Whitehead Institute/MIT Center
for Genome Research, Cambridge, Mass.; DOE's Joint
Genome Institute, Walnut Creek, Calif.; and The
Wellcome Trust Sanger Institute near Cambridge,
England.
"The enormity of the Human Genome Project is
unprecedented in biology. The international vision and
collaboration of the scientists involved played a
crucial role in the project's success," said Mark
Walport, M.D., director designate of The Wellcome
Trust, which led the Human Genome Project in the
United Kingdom. "The genome is the common thread that
connects us all, so it is only fitting that the
sequence has been given to us by scientists from all
corners of the earth."
All of the sequence data generated by the Human Genome
Project has been swiftly deposited into public
databases and made freely available to scientists
around the world, with no restrictions on its use or
redistribution. The information is scanned daily by
researchers in academia and industry, as well as by
commercial database companies providing information
services to biotechnologists.
"From the beginning, one of the operating principles
of the Human Genome Project has been that the data and
resources it has generated should rapidly be made
available to the entire scientific community," said
Robert Waterston, M.D., Ph.D., of the University of
Washington, Seattle. "Not only does the rapid release
of data promote the best interests of science, it also
maximizes the benefits that the public receives from
such research."
In 1996, at a meeting in Bermuda, Dr. Waterston and
John Sulston, Ph.D., then director of the Sanger
Centre (now The Wellcome Trust Sanger Institute), led
the International Human Genome Sequencing Consortium
to adopt the so-called "Bermuda Principles," which
expressly call for automatic, rapid release of
sequence assemblies of 2,000 bases or greater to the
public domain.
Scientists have been quick to mine this new trove of
genomic data, as well as to utilize the genomic tools
and technologies developed by the Human Genome
Project. For example, when the Human Genome Project
began in 1990, scientists had discovered fewer than
100 human disease genes. Today, more than 1,400
disease genes have been identified.
For scientists seeking to understand the role of
genetics in human health and disease, the Human Genome
Project's finished sequence represents a significant
advance over the "working draft" that was announced in
June 2000. The working draft covered 90 percent of the
gene-containing part of the sequence, 28 percent of
which had reached finished form, and contained about
150,000 gaps. The finished version of the human genome
now contains 99 percent of the gene-containing
sequence, with the missing parts essentially contained
in less than 400 defined gaps.
These remaining gaps represent regions of DNA in the
genome with unusual structures that cannot be reliably
sequenced with current technology. These regions,
however, appear to contain very few genes. Closing
these gaps will require individual research projects
and new technologies, rather than industrial-scale
efforts of the Human Genome Project. The
high-throughput sequencing of the human genome has
thus reached its natural conclusion.
"This is the day that our planning group dreamed of,"
said Bruce Alberts, Ph.D., chairman of the 1988
National Research Council Committee on Mapping and
Sequencing the Human Genome, which produced the
original recommendations for the Human Genome Project.
"And the quality of the sequence would have amazed us.
In 1988, we weren't sure that accuracy rates of 99.9
percent were possible, and we were uncertain that
continuity over distances of millions of base pairs
could be achieved. The finished human sequence is a
fabulous outcome. Biomedical researchers now have
tremendous foundation on which to build the science
and medicine of the 21st century." Dr. Alberts is now
the president of the National Academy of Sciences.
In addition to the improved accuracy, the average DNA
letter now sits on a stretch of 27,332,000 base pairs
of uninterrupted, high-quality sequence - about 334
times longer than the 81,900 base-pair stretch that
was available in the working draft. Access to
uninterrupted stretches of sequenced DNA can make a
major difference to researchers hunting for genes,
dramatically cutting the effort and expense required
to search regions of the human genome that may contain
small and often rare mutations involved in disease.
"The Human Genome Project represents one of the
remarkable achievements in the history of science. Its
culmination this month signals the beginning of a new
era in biomedical research," said Eric Lander, Ph.D.,
director of the Whitehead-MIT Center for Genome
Research. "Biology is being transformed into an
information science, able to take comprehensive global
views of biological systems. With knowledge of all the
components of the cells, we will be able to tackle
biological problems at their most fundamental level."
The essentially complete version of the human genome
sequence also represents a major boon to the growing
field of comparative genomics: researchers are
attempting to learn more about human genetic makeup
and function by comparing our genomic sequence to that
of other organisms, such as the mouse, the rat or even
the fruit fly.
"One of the most powerful tools for understanding our
own genome is to study it within the context of a much
larger framework. That framework is being created by
ongoing efforts to sequence and analyze the genomes of
many other organisms," said Richard Gibbs, Ph.D.,
director of Baylor College of Medicine's Human Genome
Sequencing Center. "As we identify the similarities -
and the differences - among the genes of mammals and
other organisms, we will begin to gain valuable new
insights into human evolution, as well as human health
and disease."
The impact of the Human Genome Project, however,
extends far beyond laboratory analysis. Under the
guidance of Dr. Watson, the Human Genome Project
became the first large scientific undertaking to
dedicate a portion of its budget for research to the
ethical, legal and social implications (ELSI) of its
work. NHGRI and DOE each set aside 3 to 5 percent of
their genome budgets to study how the exponential
increase in knowledge about human genetic make-up may
affect individuals, institutions and society. An
example of how ELSI research has helped to inform
public policy is the fact that more than 40 states in
the United States have passed genetic
non-discrimination bills, many based on model language
that grew out of this research. These efforts will be
even more crucial in the coming years as the results
of genomic research begin to appear in the clinic.
"Achieving the goals of the Human Genome Project is a
historic milestone. But this is no time to rest and
relax," said Dr. Collins. "With this foundation of
knowledge firmly in place, the medical advances
promised from the project can now be significantly
accelerated."
To spur such acceleration, NHGRI's "A Vision for the
Future of Genomics Research" sets forth a series of
"Grand Challenges" intended to energize the scientific
community in using the newfound understanding of the
genome to uncover the causes of disease and to develop
bold new approaches to the prevention and treatment of
disease. The plan was the outcome of more than a year
of intense discussions with nearly 600 scientific and
public leaders from government, academia, non-profit
organizations and the private sector.
In the publication in Nature, the challenges facing
genomic research are depicted as a three-story house
rising from the foundation of the Human Genome
Project. The three floors, representing the three
major thrusts of this new vision - Genomics to
Biology, Genomics to Health and Genomics to Society -
are interconnected by vertical supports, representing
computational biology, ELSI, education, training,
technology development and resources. (Nature, April
14, 2003, online publication)
Many of the challenges in the vision are aimed at
utilizing genome research to combat disease and
improve human health. The recommendations include
calls for researchers to work toward:
* New tools to allow discovery in the near future
of the hereditary contributions to common diseases,
such as diabetes, heart disease and mental illness.
* New methods for the early detection of disease.
* New technologies that can sequence the entire
genome of any person for less than $1,000.
* Wider access to tools and technologies of "chemical
genomics" to improve the understanding of biological
pathways and accelerate drug discovery.
NHGRI and its partners in genome research have already
begun tackling a number of these challenges. For
example, in November 2002, a team of researchers from
six nations launched the International HapMap Project,
an effort to produce a map of common human genetic
variations aimed at speeding the search for genes that
contribute to cancer, diabetes, heart disease,
schizophrenia and many other common conditions.
"The completion of the Human Genome Project should not
be viewed as an end in itself. Rather, it marks the
start of an exciting new era - the era of the genome
in medicine and health," said Dr. Collins. "We firmly
believe the best is yet to come, and we urge all
scientists and people around the globe to join us in
turning this vision into reality."
NHGRI's U.S. partner in the Human Genome Project, DOE,
has also developed its own forward-looking plan for
genome research. The DOE plan, published in the April
11 issue of the journal Science, is focused on
understanding the ways in which microbes can provide
new opportunities for developing clean energy,
reducing climate change and cleaning the environment.
To achieve that vision, DOE has begun the "Genomes to
Life" program, which will combine research in biology,
engineering and computation with the development of
novel facilities for high-throughput biology projects.
NHGRI is one of the 27 institutes and centers at the
National Institutes of Health, an agency of the
Department of Health and Human Services (DHHS).
Additional information about NHGRI can be found at its
Web site, www.genome.gov.
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